Our primary goal is to explore the complex relationships of genetic architecture and environment in the development of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). These stroke subtypes occur in 55,000 to 60,000 persons in the U.S. each year, of whom 40 percent die within 30 days. The primary hypotheses of this ongoing study are: (1) the genetic and environmental factors associated with spontaneous ICH vary with the location and presumed mechanisms of arterial rupture; and (2) the impact of environmental and genetic risk factors for spontaneous ICH and SAH in the population vary by gender and race. We will have identified, extensively interviewed, and obtained genetic material from 1000 cases of ICH and SAH and 2000 age, gender, and race-matched controls from the Greater Cincinnati population by 2007 (540 cases and 1102 controls as of 8/31/01). Whole genome amplification of DNA abstracted from buccal cells and blood samples will be performed to maximize the usefulness of currently available DNA. Polymerase chain reactions will be performed to examine susceptibility genes that may risk factors for ICH and SAH. These include genes potentially related to the accumulation of amyloid protein in cortical blood vessels, genes related to hypertension, and genes related to the regulation of elastase (a-1-antitrypsin gene) and elastin. We will then determine the population attributable risks of ICH and SAH for environmental and genetic risk factors for the population as a whole, as well as by gender and race. With the just completed mapping of the human genome, our prospective, population-based, case-control database provides a unique resource to identify the genetic architecture and environmental factors associated with an increased risk of ICH and SAH.